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Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko Aug 2020

Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko

Faculty, Staff and Students Publications

OBJECTIVE: Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA.

METHODS: Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee …


Combinatorial Pharmacogenomic Algorithm Is Predictive Of Citalopram And Escitalopram Metabolism In Patients With Major Depressive Disorder, Richard C. Shelton, Charles R. Conway, Et Al. Aug 2020

Combinatorial Pharmacogenomic Algorithm Is Predictive Of Citalopram And Escitalopram Metabolism In Patients With Major Depressive Disorder, Richard C. Shelton, Charles R. Conway, Et Al.

2020-Current year OA Pubs

Pharmacogenomic tests used to guide clinical treatment for major depressive disorder (MDD) must be thoroughly validated. One important assessment of validity is the ability to predict medication blood levels, which reflect altered metabolism. Historically, the metabolic impact of individual genes has been evaluated; however, we now know that multiple genes are often involved in medication metabolism. Here, we evaluated the ability of individual pharmacokinetic genes (CYP2C19, CYP2D6, CYP3A4) and a combinatorial pharmacogenomic test (GeneSight Psychotropic®; weighted assessment of all three genes) to predict citalopram/escitalopram blood levels in patients with MDD. Patients from the Genomics Used to Improve DEpression Decisions (GUIDED) …


The Efficacy Of Lenvatinib Plus Everolimus In Patients With Metastatic Renal Cell Carcinoma Exhibiting Primary Resistance To Front-Line Targeted Therapy Or Immunotherapy, Lana Hamieh, Rachel L Beck, Valerie H Le, James J Hsieh Aug 2020

The Efficacy Of Lenvatinib Plus Everolimus In Patients With Metastatic Renal Cell Carcinoma Exhibiting Primary Resistance To Front-Line Targeted Therapy Or Immunotherapy, Lana Hamieh, Rachel L Beck, Valerie H Le, James J Hsieh

2020-Current year OA Pubs

BACKGROUND: Patients with primary refractory metastatic renal cell carcinoma (mRCC) have a dismal prognosis and poor response to subsequent treatments. While there are several approved second-line therapies, it remains critical to choose the most effective treatment regimen.

PATIENTS AND METHODS: We identified 7 patients with clear cell mRCC who had primary resistance to vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitor (ICI) combination therapy. The patients were treated with lenvatinib (a multitargeted TKI) plus everolimus (a mammalian target of rapamycin inhibitor). Among these 7 patients, 2 had prior TKI therapy, 3 had prior ICI therapy, …


Out-Patient Neurological Disorders In Tanzania: Experience From A Private Institution In Dar Es Salaam, Philip Adebayo, Omar Aziz, Rose E. Mwakabatika, Mandela Makakala, Mugisha Clement, Shabbir Adamjee, Noureen Mushi, Ahmed Jusabani, Eric Aris Aug 2020

Out-Patient Neurological Disorders In Tanzania: Experience From A Private Institution In Dar Es Salaam, Philip Adebayo, Omar Aziz, Rose E. Mwakabatika, Mandela Makakala, Mugisha Clement, Shabbir Adamjee, Noureen Mushi, Ahmed Jusabani, Eric Aris

Internal Medicine, East Africa

Background and introduction: Low and middle-income countries (LMIC) have a considerable burden of neurological disorders. Available profile of neurological disorders in our environment is biased towards neurological admissions. There is a paucity of data on out-patient neurological conditions in sub-Saharan Africa.

Objective: To determine the frequency and demographic data of neurological illnesses being managed at the adult out-patient neurology clinic of the Aga Khan Hospital, Dar es Salaam (AKHD).

Materials and methods: The electronic medical records of all cases with neurological diseases who presented to the adult neurology clinic of the AKHD between January 2018, and December 2019 were retrospectively …


Myocardial Infarction Can Be Safely Excluded By High-Sensitivity Troponin I Testing 3 Hours After Emergency Department Presentation., W Frank Peacock, Robert Christenson, Deborah B Diercks, Christian Fromm, Gary F Headden, Christopher J Hogan, Erik B Kulstad, Frank Lovecchio, Richard M Nowak, Jon W Schrock, Adam J Singer, Alan B Storrow, Joely Straseski, Alan H B Wu, Daniel P Zelinski Aug 2020

Myocardial Infarction Can Be Safely Excluded By High-Sensitivity Troponin I Testing 3 Hours After Emergency Department Presentation., W Frank Peacock, Robert Christenson, Deborah B Diercks, Christian Fromm, Gary F Headden, Christopher J Hogan, Erik B Kulstad, Frank Lovecchio, Richard M Nowak, Jon W Schrock, Adam J Singer, Alan B Storrow, Joely Straseski, Alan H B Wu, Daniel P Zelinski

Heart and Vascular Articles

BACKGROUND: The accuracy and speed by which acute myocardial infarction (AMI) is excluded are an important determinant of emergency department (ED) length of stay and resource utilization. While high-sensitivity troponin I (hsTnI) >99th percentile (upper reference level [URL]) represents a "rule-in" cutpoint, our purpose was to evaluate the ability of the Beckman Coulter hsTnI assay, using various level-of-quantification (LoQ) cutpoints, to rule out AMI within 3 hours of ED presentation in suspected acute coronary syndrome (ACS) patients.

METHODS: This multicenter evaluation enrolled adults with >5 minutes of ACS symptoms and an electrocardiogram obtained per standard care. Exclusions were ST-segment elevation …


Predicting Quality Of Clinical Performance From Cardiology Fellowship Applications, Michael W Cullen, Thomas J Beckman, Kristine M Baldwin, Gregory J Engstler, Jay Mandrekar, Christopher G Scott, Kyle W Klarich Aug 2020

Predicting Quality Of Clinical Performance From Cardiology Fellowship Applications, Michael W Cullen, Thomas J Beckman, Kristine M Baldwin, Gregory J Engstler, Jay Mandrekar, Christopher G Scott, Kyle W Klarich

The Texas Heart Institute Journal

Variables in cardiology fellowship applications have not been objectively analyzed against applicants' subsequent clinical performance. We investigated possible correlations in a retrospective cohort study of 65 cardiology fellows at the Mayo Clinic (Rochester, Minn) who began 2 years of clinical training from July 2007 through July 2013. Application variables included the strength of comparative statements in recommendation letters and the authors' academic ranks, membership status in the Alpha Omega Alpha Honor Medical Society, awards earned, volunteer activities, United States Medical Licensing Examination (USMLE) scores, advanced degrees, publications, and completion of a residency program ranked in the top 6 in the …


Mechanical Prosthetic Valve Sparing For Aortic Root Abscess Complicated By Infective Endocarditis, Ahmed Ahmed, Ayman Ammar, Yasser Elnahas, Mohammed Abd Al Jawad Aug 2020

Mechanical Prosthetic Valve Sparing For Aortic Root Abscess Complicated By Infective Endocarditis, Ahmed Ahmed, Ayman Ammar, Yasser Elnahas, Mohammed Abd Al Jawad

The Texas Heart Institute Journal

Aortic root abscess complicated by infective endocarditis of a mechanical prosthetic valve is associated with morbidity and death. We retrospectively report our experience with a valve-sparing technique for managing this condition.

From October 2014 through November 2017, 41 patients at our center underwent surgery for aortic root abscess complicated by infective endocarditis of a mechanical prosthetic valve. Twenty (48.7%) met prespecified criteria for use of our valve-sparing technique after careful assessment of the mechanical valve and surrounding tissues. Our technique involved draining the abscess, aggressively débriding all infected and necrotic tissues, and then repairing the resulting defect by suturing a …


Association Of Tph1 And Serotonin Transporter Genotypes With Treatment Response For Suicidal Ideation: A Preliminary Study, David A Nielsen, Huiqiong Deng, Michelle A Patriquin, Mark J Harding, John Oldham, Ramiro Salas, J Christopher Fowler, B Christopher Frueh Aug 2020

Association Of Tph1 And Serotonin Transporter Genotypes With Treatment Response For Suicidal Ideation: A Preliminary Study, David A Nielsen, Huiqiong Deng, Michelle A Patriquin, Mark J Harding, John Oldham, Ramiro Salas, J Christopher Fowler, B Christopher Frueh

Staff and Researcher Publications

Variants in three genes coding for components of the serotonergic system, the tryptophan hydroxylase 1 (TPH1) rs1799913, serotonin transporter (SLC6A4) 5-HTTLPR, and serotonin receptor 2A (HTR2A) rs6311, were evaluated for association with suicidal ideation (SI) and with recovery from SI in a psychiatric inpatient population. Five hundred and eighty-two adult inpatients, including 390 patients who had SI, collected from December 2012 to April 2016 were assessed. SI recovery, calculated as change in SI between the first two-week period after admission and weeks 5 and 6, was appraised for association with the three variants. In this preliminary study, both TPH1 and …


Importance Of Persistent Right-To-Left Shunt After Patent Foramen Ovale Closure In Cryptogenic Stroke Patients, Lu He, Gesheng Cheng, Yajuan Du, Yushun Zhang Aug 2020

Importance Of Persistent Right-To-Left Shunt After Patent Foramen Ovale Closure In Cryptogenic Stroke Patients, Lu He, Gesheng Cheng, Yajuan Du, Yushun Zhang

The Texas Heart Institute Journal

Percutaneous closure of patent foramen ovale (PFO) is widely performed to prevent recurrent stroke or transient ischemic attack in patients with cryptogenic stroke. However, the influence of different degrees of right-to-left shunting (RLS) has rarely been reported.

We retrospectively evaluated the cases of 268 patients with cryptogenic stroke who underwent PFO closure at our hospital from April 2012 through April 2015. In accordance with RLS severity, we divided the patients into 2 groups: persistent RLS during normal breathing and the Valsalva maneuver (n=112) and RLS only during the Valsalva maneuver (n=156). Baseline characteristics, morphologic features, and procedural and follow-up data …


The Brief Case: "Not Positive" Or "Not Sure"-Covid-19-Negative Results In A Symptomatic Patient, Bijal A Parikh, Thomas C Bailey, Patrick G Lyons, Neil W Anderson Jul 2020

The Brief Case: "Not Positive" Or "Not Sure"-Covid-19-Negative Results In A Symptomatic Patient, Bijal A Parikh, Thomas C Bailey, Patrick G Lyons, Neil W Anderson

Open Access Publications

No abstract provided.


Characterization Of A Multicenter Pediatric-Hydrocephalus Shunt Biobank, Jacob Gluski, Paul Zajciw, Prashant Hariharan, Amanda Morgan, Diego M Morales, Andrew Jea, William Whitehead, Neena Marupudi, Steven Ham, Sandeep Sood, James P Mcallister Ii, David D Limbrick Jr, Carolyn A Harris Jul 2020

Characterization Of A Multicenter Pediatric-Hydrocephalus Shunt Biobank, Jacob Gluski, Paul Zajciw, Prashant Hariharan, Amanda Morgan, Diego M Morales, Andrew Jea, William Whitehead, Neena Marupudi, Steven Ham, Sandeep Sood, James P Mcallister Ii, David D Limbrick Jr, Carolyn A Harris

Open Access Publications

BACKGROUND: Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank.

METHODS: To date, four hospital centers have contributed various components of failed shunts and CSF from patients …


Trial Of Roflumilast Cream For Chronic Plaque Psoriasis, Mark G. Lebwohl, Kim A. Papp, Linda F. Stein Gold, Melinda J. Gooderham, Leon H. Kircik, Zoe D. Draelos, Steven E. Kempers, Mathew Zirwas, Kathleen Smith, David W. Osborne, Marie-Louise Trotman, Lynn Navale, Charlotte Merritt, David R. Berk, Howard Welgus Jul 2020

Trial Of Roflumilast Cream For Chronic Plaque Psoriasis, Mark G. Lebwohl, Kim A. Papp, Linda F. Stein Gold, Melinda J. Gooderham, Leon H. Kircik, Zoe D. Draelos, Steven E. Kempers, Mathew Zirwas, Kathleen Smith, David W. Osborne, Marie-Louise Trotman, Lynn Navale, Charlotte Merritt, David R. Berk, Howard Welgus

Dermatology Articles

BACKGROUND: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.

METHODS: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a …


The Influence Of Telehealth For Better Health Across Communities., Jane A. Mcelroy, Tamara M. Day, Mirna Becevic Jul 2020

The Influence Of Telehealth For Better Health Across Communities., Jane A. Mcelroy, Tamara M. Day, Mirna Becevic

Project ECHO Bibliography

Rapid spread of coronavirus disease 2019 (COVID-19) forced an abrupt shift in the traditional US health care delivery model to meet the needs of patients, staff, and communities. Through federal policy changes on telehealth, patient care shifted from in-person to telephone or video visits, and health care providers reached out to patients most at risk for exacerbation of chronic disease symptoms. ECHO (Extension for Community Healthcare Outcomes), a videoconferencing peer learning application, engaged health care providers across Missouri in the treatment and management of complex COVID-19-positive patients. Re-envisioning health care in the digital age includes robust utilization of telehealth to …


Reduced Intensity Conditioning For Acute Myeloid Leukemia Using Melphalan- Vs Busulfan-Based Regimens: A Cibmtr Report, Zheng Zhou, Rajneesh Nath, Jan Cerny, Hai-Lin Wang, Mei-Jie Zhang, Hisham Abdel-Azim, Vaibhav Agrawal, Gulrayz Ahmed, A Samer Al-Homsi, Mahmoud Aljurf, Hassan B Alkhateeb, Amer Assal, Ulrike Bacher, Ashish Bajel, Qaiser Bashir, Minocher Battiwalla, Vijaya Raj Bhatt, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Hannah Choe, Edward Copelan, Corey Cutler, Moussab B Damlaj, Zachariah Defilipp, Marcos De Lima, Miguel Angel Diaz, Nosha Farhadfar, James Foran, César O Freytes, Aaron T Gerds, Usama Gergis, Michael R Grunwald, Zartash Gul, Mehdi Hamadani, Shahrukh Hashmi, Mark Hertzberg, Gerhard C Hildebrandt, Nasheed Hossain, Yoshihiro Inamoto, Luis Isola, Tania Jain, Rammurti T Kamble, Muhammad Waqas Khan, Mohamed A Kharfan-Dabaja, Partow Kebriaei, Natasha Kekre, Nandita Khera, Hillard M Lazarus, Jane L Liesveld, Mark Litzow, Hongtao Liu, David I Marks, Rodrigo Martino, Vikram Mathews, Asmita Mishra, Hemant S Murthy, Arnon Nagler, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Rebecca Olin, Richard F Olsson, Neil Palmisiano, Sagar S Patel, Mrinal M Patnaik, Attaphol Pawarode, Miguel-Angel Perales, Ioannis Politikos, Uday Popat, David Rizzieri, Brenda M Sandmaier, Bipin N Savani, Sachiko Seo, Nirav N Shah, Geoffrey L Uy, David Valcárcel, Leo F Verdonck, Edmund K Waller, Youjin Wang, Daniel Weisdorf, Baldeep Wirk, Eric Wong, Jean A Yared, Wael Saber Jul 2020

Reduced Intensity Conditioning For Acute Myeloid Leukemia Using Melphalan- Vs Busulfan-Based Regimens: A Cibmtr Report, Zheng Zhou, Rajneesh Nath, Jan Cerny, Hai-Lin Wang, Mei-Jie Zhang, Hisham Abdel-Azim, Vaibhav Agrawal, Gulrayz Ahmed, A Samer Al-Homsi, Mahmoud Aljurf, Hassan B Alkhateeb, Amer Assal, Ulrike Bacher, Ashish Bajel, Qaiser Bashir, Minocher Battiwalla, Vijaya Raj Bhatt, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Hannah Choe, Edward Copelan, Corey Cutler, Moussab B Damlaj, Zachariah Defilipp, Marcos De Lima, Miguel Angel Diaz, Nosha Farhadfar, James Foran, César O Freytes, Aaron T Gerds, Usama Gergis, Michael R Grunwald, Zartash Gul, Mehdi Hamadani, Shahrukh Hashmi, Mark Hertzberg, Gerhard C Hildebrandt, Nasheed Hossain, Yoshihiro Inamoto, Luis Isola, Tania Jain, Rammurti T Kamble, Muhammad Waqas Khan, Mohamed A Kharfan-Dabaja, Partow Kebriaei, Natasha Kekre, Nandita Khera, Hillard M Lazarus, Jane L Liesveld, Mark Litzow, Hongtao Liu, David I Marks, Rodrigo Martino, Vikram Mathews, Asmita Mishra, Hemant S Murthy, Arnon Nagler, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Rebecca Olin, Richard F Olsson, Neil Palmisiano, Sagar S Patel, Mrinal M Patnaik, Attaphol Pawarode, Miguel-Angel Perales, Ioannis Politikos, Uday Popat, David Rizzieri, Brenda M Sandmaier, Bipin N Savani, Sachiko Seo, Nirav N Shah, Geoffrey L Uy, David Valcárcel, Leo F Verdonck, Edmund K Waller, Youjin Wang, Daniel Weisdorf, Baldeep Wirk, Eric Wong, Jean A Yared, Wael Saber

Faculty, Staff and Students Publications

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival …


Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al Jul 2020

Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al

Open Access Publications

Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) …


Proteogenomic Characterization Reveals Therapeutic Vulnerabilities In Lung Adenocarcinoma, Michael A. Gillette, Song Cao, Yize Li, Wen-Wei Liang, Michael C Wendl, Ramaswamy Govindan, Et Al. Jul 2020

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities In Lung Adenocarcinoma, Michael A. Gillette, Song Cao, Yize Li, Wen-Wei Liang, Michael C Wendl, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. …


Pathophysiology Of Hyperkalemia Presenting As Brugada Pattern On Electrocardiogram (Ecg), Benjamin Doty, Elaine Kim, Jeremiah T. Phelps, Peter Akpunonu Jul 2020

Pathophysiology Of Hyperkalemia Presenting As Brugada Pattern On Electrocardiogram (Ecg), Benjamin Doty, Elaine Kim, Jeremiah T. Phelps, Peter Akpunonu

Emergency Medicine Faculty Publications

BACKGROUND Brugada phenocopies (BrP) are clinical and electrocardiographic (ECG) entities elicited by reversible medical conditions speculated to have pathogenesis rooted in ion current imbalances or conduction delays within the myocardial wall. During an inciting pathologic condition, it produces ECG patterns identical to those of congenitally-acquired Brugada syndrome and subsequently returns to normal ECG patterns upon resolution of the medical condition. This case report describes a 26-year-old man presenting to the Emergency Department (ED) for suspected heroin overdose with a rare ECG consistent with BrP secondary to acute hyperkalemia.

CASE REPORT A 26-year-old man with a history of substance abuse and …


Comparison Of Tissue Molecular Biomarker Testing Turnaround Times And Concordance Between Standard Of Care And The Biocartis Idylla Platform In Patients With Colorectal Cancer, Gregory J. Tsongalis, M Rabie Al Turkmani, Michael Suriawinata, Michael J. Babcock, Kristi Mitchell, Yi Ding, Lisa Scicchitano, Adrian Tira, Lela Buckingham, Sara Atkinson, Amy Lax, Dara L. Aisner, Kurtis D. Davies, Holly N. Wood, Stacey S. O'Neill, Edward A. Levine, Judy Sequeira, Shuko Harada, Gina Defrank, Ravikumar Paluri, Bradford A. Tan, Heather Colabella, Christopher Snead, Marcia Cruz-Correa, Virginia Ramirez, Arnaldo Rojas, Huiya Huang, Alexander C. Mackinnon, Fernando U. Garcia, Sharon M. Cavone, Mutasim Elfahal, Gyorgy Abel, Mohammad A. Vasef, Andrew Judd, Mark W. Linder, Khaled Alkhateeb, William L. Skinner, Ralph Boccia, Kashyap Patel Jul 2020

Comparison Of Tissue Molecular Biomarker Testing Turnaround Times And Concordance Between Standard Of Care And The Biocartis Idylla Platform In Patients With Colorectal Cancer, Gregory J. Tsongalis, M Rabie Al Turkmani, Michael Suriawinata, Michael J. Babcock, Kristi Mitchell, Yi Ding, Lisa Scicchitano, Adrian Tira, Lela Buckingham, Sara Atkinson, Amy Lax, Dara L. Aisner, Kurtis D. Davies, Holly N. Wood, Stacey S. O'Neill, Edward A. Levine, Judy Sequeira, Shuko Harada, Gina Defrank, Ravikumar Paluri, Bradford A. Tan, Heather Colabella, Christopher Snead, Marcia Cruz-Correa, Virginia Ramirez, Arnaldo Rojas, Huiya Huang, Alexander C. Mackinnon, Fernando U. Garcia, Sharon M. Cavone, Mutasim Elfahal, Gyorgy Abel, Mohammad A. Vasef, Andrew Judd, Mark W. Linder, Khaled Alkhateeb, William L. Skinner, Ralph Boccia, Kashyap Patel

Pathology Research and Scholarship

OBJECTIVES: Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti-epidermal growth factor receptor therapy and BRAF testing for prognostic stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories.

METHODS: Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods.

RESULTS: There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain …


Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk Jul 2020

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …


Screening And Treatment Outcomes In Adults And Children With Type 1 Diabetes And Asymptomatic Celiac Disease: The Cd-Diet Study., Farid H Mahmud, Antoine B M Clarke, Kariym C Joachim, Esther Assor, Charlotte Mcdonald, Fred Saibil, Heather A Lochnan, Zubin Punthakee, Amish Parikh, Andrew Advani, Baiju R Shah, Bruce A Perkins, Caroline S Zuijdwijk, David R Mack, Dror Koltin, Emilia N De Melo, Eugene Hsieh, Geetha Mukerji, Jeremy Gilbert, Kevin Bax, Margaret L Lawson, Maria Cino, Melanie D Beaton, Navaaz A Saloojee, Olivia Lou, Patricia H Gallego, Premysl Bercik, Robyn L Houlden, Ronnie Aronson, Susan E Kirsch, William G Paterson, Margaret A Marcon Jul 2020

Screening And Treatment Outcomes In Adults And Children With Type 1 Diabetes And Asymptomatic Celiac Disease: The Cd-Diet Study., Farid H Mahmud, Antoine B M Clarke, Kariym C Joachim, Esther Assor, Charlotte Mcdonald, Fred Saibil, Heather A Lochnan, Zubin Punthakee, Amish Parikh, Andrew Advani, Baiju R Shah, Bruce A Perkins, Caroline S Zuijdwijk, David R Mack, Dror Koltin, Emilia N De Melo, Eugene Hsieh, Geetha Mukerji, Jeremy Gilbert, Kevin Bax, Margaret L Lawson, Maria Cino, Melanie D Beaton, Navaaz A Saloojee, Olivia Lou, Patricia H Gallego, Premysl Bercik, Robyn L Houlden, Ronnie Aronson, Susan E Kirsch, William G Paterson, Margaret A Marcon

Paediatrics Publications

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD.

RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA

RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%,

CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.


A Foldable Nonpenetrating Keratoprosthesis: Medium To Long-Term Clinical Results In Patients With Corneal Blindness Due To Noninflammatory Anterior Cornea Disease., Jose M Vargas, Eric Shiuey Jul 2020

A Foldable Nonpenetrating Keratoprosthesis: Medium To Long-Term Clinical Results In Patients With Corneal Blindness Due To Noninflammatory Anterior Cornea Disease., Jose M Vargas, Eric Shiuey

Department of Medicine Faculty Papers

PURPOSE: To report the medium to long-term safety and performance outcomes of the KeraKlear nonpenetrating artificial cornea (KeraKlear) as the primary procedure in patients with corneal blindness due to noninflammatory anterior cornea disease.

METHODS: Fifteen patients with corneal blindness (preoperative visual acuity [VA] of ≥20/200) due to a non-inflammatory anterior corneal condition were included in this prospective, single-center study. Preoperative diagnoses included corneal scars, keratoconus, and corneal dystrophies. Diseased corneas were implanted with the KeraKlear (KeraMed Inc., Irvine, California, USA) by a single surgeon (JMV) using a femtosecond laser to create all incisions. Participants were followed up with for as …


Development Of The Uncertainty Communication Checklist: A Patient-Centered Approach To Patient Discharge From The Emergency Department, Kristin L. Rising, Rhea E. Powell, Kenzie A Cameron, David H Salzman, Dimitrios Papanagnou, Amanda Doty, Lori Latimer, Katherine Piserchia, William C Mcgaghie, Danielle M Mccarthy Jul 2020

Development Of The Uncertainty Communication Checklist: A Patient-Centered Approach To Patient Discharge From The Emergency Department, Kristin L. Rising, Rhea E. Powell, Kenzie A Cameron, David H Salzman, Dimitrios Papanagnou, Amanda Doty, Lori Latimer, Katherine Piserchia, William C Mcgaghie, Danielle M Mccarthy

Department of Emergency Medicine Faculty Papers

Clear communication with patients upon emergency department (ED) discharge is important for patient safety during the transition to outpatient care. Over one-third of patients are discharged from the ED with diagnostic uncertainty, yet there is no established approach for effective discharge communication in this scenario. From 2017 to 2019, the authors developed the Uncertainty Communication Checklist for use in simulation-based training and assessment of emergency physician communication skills when discharging patients with diagnostic uncertainty. This development process followed the established 12-step Checklist Development Checklist framework and integrated patient feedback into 6 of the 12 steps. Patient input was included as …


Physiological Factors Of Female Runners With And Without Stress Fracture Histories: A Pilot Study., Therese E Johnston, Colleen Dempsey, Frances Gilman, Ryan Tomlinson, Ann-Katrin Jacketti, Jeremy Close Jul 2020

Physiological Factors Of Female Runners With And Without Stress Fracture Histories: A Pilot Study., Therese E Johnston, Colleen Dempsey, Frances Gilman, Ryan Tomlinson, Ann-Katrin Jacketti, Jeremy Close

Department of Physical Therapy Faculty Papers

BACKGROUND: Female runners are at increased risk of stress fractures (SFs) compared with men. Literature is lacking with regard to best practice for preventing and treating SFs in women. The purpose of the study was to compare physiological measures and running-related factors between women of various ages and running abilities with and without a history of running-related SFs.

HYPOTHESIS: Women with and without SF histories will differ with regard to medical and menstrual history, bone health, body composition, nutrition, and running history.

STUDY DESIGN: Prospective cohort study.

LEVEL OF EVIDENCE: Level 2.

METHODS: A total of 20 female runners with …


Association Of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (Covid-19), Pierre Francois Laterre, Bruno François, Christine Collienne, Philippe Hantson, Robin Jeannet, Kenneth E. Remy, Richard S. Hotchkiss Jul 2020

Association Of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (Covid-19), Pierre Francois Laterre, Bruno François, Christine Collienne, Philippe Hantson, Robin Jeannet, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

No abstract provided.


Maternal Knowledge Of The Risk Of Vertical Transmission And Offspring Acquisition Of Hepatitis B., Mauricio Lisker-Melman, Mandana Khalili, Steven H Belle, Norah A Terrault, Hsing-Hua S Lin, Coleman I Smith, Raymond T Chung, Naoky Tsai, Natalie H Bzowej, Tram T Tran, Sarah Jane Schwarzenberg, Hepatitis B Research Network (Hbrn) Jul 2020

Maternal Knowledge Of The Risk Of Vertical Transmission And Offspring Acquisition Of Hepatitis B., Mauricio Lisker-Melman, Mandana Khalili, Steven H Belle, Norah A Terrault, Hsing-Hua S Lin, Coleman I Smith, Raymond T Chung, Naoky Tsai, Natalie H Bzowej, Tram T Tran, Sarah Jane Schwarzenberg, Hepatitis B Research Network (Hbrn)

Open Access Publications

INTRODUCTION AND OBJECTIVES: Universal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B.

MATERIALS AND METHODS: The Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) …


Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra Jul 2020

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …


Impact Of Vancomycin-Induced Changes In The Intestinal Microbiota On The Pharmacokinetics Of Simvastatin, Jung Sunwoo, Sang Chun Ji, Andrew Hyoungjin Kim, Kyung-Sang Yu, Joo-Youn Cho, In-Jin Jang, Seunghwan Lee Jul 2020

Impact Of Vancomycin-Induced Changes In The Intestinal Microbiota On The Pharmacokinetics Of Simvastatin, Jung Sunwoo, Sang Chun Ji, Andrew Hyoungjin Kim, Kyung-Sang Yu, Joo-Youn Cho, In-Jin Jang, Seunghwan Lee

2020-Current year OA Pubs

The pharmacokinetic (PK) properties of drugs are affected in several ways by interactions with microbiota. The aim of this study was to investigate the effects of oral vancomycin on the gut microbiota and, consequently, on the PKs of simvastatin. An open-label, single arm, sequential crossover study was conducted in six healthy Korean male subjects. After 6 days on a control diet, simvastatin 40 mg was orally administered to the subjects before and after 1 week of oral vancomycin treatment. Blood samples for PK analysis and fecal samples for metagenomic and metabolomic analyses were collected. After vancomycin treatment, the richness of …


A Domain-General Cognitive Core Defined In Multimodally Parcellated Human Cortex, Moataz Assem, Matthew F Glasser, David C Van Essen, John Duncan Jun 2020

A Domain-General Cognitive Core Defined In Multimodally Parcellated Human Cortex, Moataz Assem, Matthew F Glasser, David C Van Essen, John Duncan

2020-Current year OA Pubs

Numerous brain imaging studies identified a domain-general or "multiple-demand" (MD) activation pattern accompanying many tasks and may play a core role in cognitive control. Though this finding is well established, the limited spatial localization provided by traditional imaging methods precluded a consensus regarding the precise anatomy, functional differentiation, and connectivity of the MD system. To address these limitations, we used data from 449 subjects from the Human Connectome Project, with the cortex of each individual parcellated using neurobiologically grounded multimodal MRI features. The conjunction of three cognitive contrasts reveals a core of 10 widely distributed MD parcels per hemisphere that …


Prevalence, Incidence, And Clearance Of Human Papillomavirus Types Covered By Current Vaccines In Men With Human Immunodeficiency Virus In The Sun Study, Pragna Patel, Tim Bush, Lois Conley, Elizabeth R Unger, Teresa M Darragh, Keith Henry, Gerome Escota, John T Brooks, Erna Milunka Kojic Jun 2020

Prevalence, Incidence, And Clearance Of Human Papillomavirus Types Covered By Current Vaccines In Men With Human Immunodeficiency Virus In The Sun Study, Pragna Patel, Tim Bush, Lois Conley, Elizabeth R Unger, Teresa M Darragh, Keith Henry, Gerome Escota, John T Brooks, Erna Milunka Kojic

2020-Current year OA Pubs

BACKGROUND: High-risk anal human papillomavirus (HPV) infection is prevalent among men living with human immunodeficiency virus (HIV); the association between 9-valent (9v) high-risk HPV (HR-HPV) vaccine types and abnormal cytology has not been well characterized.

METHODS: We followed a prospective cohort study of persons with HIV at 7 HIV clinics in 4 US cities from March 2004 through June 2012. Annually, providers collected separate anal swabs for HPV detection and cytopathologic examination. Among men, we examined prevalence, incidence, and clearance of 9v HR-HPV vaccine types, compared with other HR types, and associations with abnormal cytology to assess potential vaccine impact. …


Vitamin A And Fish Oils For Preventing The Progression Of Retinitis Pigmentosa., Stephen G. Schwartz, Xue Wang, Pamela Chavis, Ajay E. Kuriyan, Samuel A. Abariga Jun 2020

Vitamin A And Fish Oils For Preventing The Progression Of Retinitis Pigmentosa., Stephen G. Schwartz, Xue Wang, Pamela Chavis, Ajay E. Kuriyan, Samuel A. Abariga

Wills Eye Hospital Papers

BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to blindness. Symptoms may become manifest during childhood or adulthood which include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). Visual field loss is progressive and affects central vision later in the disease course. The worldwide prevalence of RP is approximately 1 in 4000, with 100,000 individuals affected in the USA. At this time, there is no proven therapy for RP.

OBJECTIVES: The objective of this review was to …